The proposed research is further development of basic optical spectroscopic models for skin and the application of this knowledge to study cutaneous photobiologic responses, improve or develop new phototherapies, and provide needed diagnostic techniques. Recently derived optical models describing radiation transfer through human skin will be refined, extended, and examined experimentally in vitro and in vivo. These models can be used to reconstruct, from noninvasive measurements, the radiation densities within each skin layer and cutaneous blood vessels. Thus, they are central to designing phototherapy and explaining any photobiologic response quantitatively. The models include absorption coefficients and concentrations of the major skin pigments as variables and will be used to measure melanin content and dermal microvascular blood volumes, both of which are altered by ultraviolet irradiation. Noninvasive monitoring of blood and tissue levels of drugs with distinctive optical absorption spectra will be examined. Pulsatile distentions of superficial cutaneous vessels can be measured optically, and will be used to noninvasively measure microvascular compliance. This is of potential importance in artersclerosis diabetes, and collagen diseases. Skin autoluminescence has never been optically examined, yet is of proven diagnostic value. We will identify the spectra and fluorophores involved. Tryptophan, demosine and other fluorophores will be studied as diagnostic probes. Two unique methods for producing and studying the phototoxic and therapeutic effects of psoralen-DNA monoadducts vs. crosslinks in humans are proposed. We have shown in humans that microvascular damage and a host of hemodynamic effects can be selectively caused by pulsed laser exposures of human skin. Our theoretical approach to both the optical and thermal transfer involved has never been used in medical application of lasers before, and its potential extends well beyond the initial goal of treating benign vascular skin tumors. We propose to complete basic studies elucidating mechanisms, and to similarly test the XeF laser as a means for producing specific pigment cell damage.